RATIONALE: Stereotactic radiosurgery may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Radiation therapy uses high-energy x rays to kill tumor cells. It is not yet known whether stereotactic radiosurgery is more effective than whole-brain radiation therapy in treating patients with brain metastases.

PURPOSE: This randomized phase III trial studies how well stereotactic radiosurgery works compared to whole-brain radiation therapy in treating patients with brain metastases after surgery.

OBJECTIVES:

Primary

• To ascertain in patients with one to four brain metastases whether there is improved overall survival in patients who receive stereotactic radiosurgery (SRS) to the surgical bed compared to patients who receive whole-brain radiotherapy (WBRT).
• To ascertain in patients with one to four brain metastases whether there is less neurocognitive progression at 6 months post-radiation in patients who receive SRS to the surgical bed compared to patients who receive WBRT.

Secondary

• To ascertain in patients with resected brain metastases whether there is improved quality-of-life (QOL) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
• To ascertain in patients with one to four brain metastases whether there is equal longer time to central nervous system (CNS) failure (brain) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
• To ascertain in patients with one to four brain metastases whether there is longer duration of functional independence in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
• To ascertain in patients with one to four brain metastases whether there is better long-term neurocognitive status in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
• To tabulate and descriptively compare the post-treatment adverse events associated with the interventions.
• To evaluate local tumor bed recurrence at 6 months with post-surgical SRS to the surgical bed in comparison to WBRT.
• To evaluate time to local recurrence with post-surgical SRS to the surgical bed in comparison to WBRT.
• To evaluate if there is any difference in CNS failure patterns (local, distant, leptomeningeal) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.

Exploratory

• To evaluate radiation changes in the limbic system that may correlate with neurotoxicity using brain MRI scans.
• To determine whether Apo E (i.e., Apo E2, Apo E3, and Apo E4) genotyping may prove to be a predictor of radiation-induced neurocognitive decline (or neuroprotection).
• To determine whether inflammatory markers (i.e., IL-1, IL-6, and TNF-α) may prove to be predictors of radiation-induced neurocognitive decline.
• To determine whether oxidative stress biomarkers (i.e., protein carbonyl content, lipid hydroperoxides, and isoprostane levels) may prove to be predictors of radiation-induced neurocognitive decline.
• To determine whether hormone and growth factors [i.e., glucocorticoids (e.g., cortisol), gonadal steroids (e.g., estradiol, testosterone, progesterone), growth hormone, human chorionic gonadotropin (hCG), insulin-like growth factor-1 (IGF-1), and neuronal growth factor (NGF)] may prove to be a predictor of radiation-induced neurocognitive decline.

OUTLINE: This is a multicenter study. Patients are stratified according to age in years (< 60 vs ≥ 60), extracranial disease controlled (≤ 3 months vs > 3 months), number of pre-operative brain metastases (1 vs 2-4), histology (lung vs radioresistant [brain metastases from a sarcoma, melanoma, or renal cell carcinoma histology] vs other), and resection cavity maximal diameter (≤ 3 cm vs > 3 cm). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo whole-brain radiotherapy (WBRT) once a day, 5 days a week, for approximately 3 weeks.
• Arm II: Patients undergo stereotactic radiosurgery (SRS) using a gamma knife or a linear accelerator procedure.

Serum, whole blood, and urine samples are collected at baseline and periodically during study for genetic markers, inflammatory markers, oxidative stress biomarkers, and hormone and growth factor studies by ELISA and other assays.

Patients complete the Functional Assessment of Cancer Therapy-Brain ( FACT-BR), the activities of daily living (ADLs), the Fatigue/Uniscale Assessment, and the Linear Analog Self Assessment (LASA) quality-of-life questionnaires at baseline and periodically during study. Neurocognitive functions, such as memory, verbal fluency, visual attention, executive function, and delayed memory, are also assessed.

After completion of study therapy, patients are followed up periodically for 5 years.

DISEASE CHARACTERISTICS:

• Four or fewer brain metastases (as defined on the pre-operative MRI brain scan) and status post resection of one of the lesions
• Pathology from the resected brain metastasis must be consistent with a non-central nervous system primary site
  • Patients with or without active disease outside the nervous system are eligible (including patients with unknown primaries), as long as the pathology from the brain is consistent with a non-central nervous system primary site
• Any unresected lesions must measure ≤ 3.0 cm in maximal extent on the contrasted pre-operative treatment MRI brain scan obtained ≤ 35 days prior to pre-registration
  • The metastases size restriction does not apply to the resected brain metastasis; with resected brain metastases only surgical cavity size determines eligibility
• Planning MRI confirmed zero, one, two or three unresected lesions
  • Each unresected lesion must measure < 3.0 cm in maximal extent on the contrasted planning MRI brain scan
  • The pre-registration brain scan may be used for the planning scan if obtained ≤ 14 days prior to randomization
• Resection cavity must measure < 5.0 cm in maximal extent on the post-operative MRI (or CT) brain scan obtained ≤ 35 days prior to pre-registration
  • The pre-registration brain scan may be used for the planning scan if obtained ≤14 days prior to randomization
  • It is permissible for the resection of a dominant brain metastasis to include a smaller "satellite" metastasis as long as the single resection cavity is less than the maximum size requirements
• All standard tumor-staging procedures necessary to define baseline extracranial disease status completed ≤ 42 days prior to pre-registration
• No primary germ cell tumor, small cell carcinoma, or lymphoma
• No widespread definitive leptomeningeal metastasis
• No brain metastasis that is located ≤ 5 mm of the optic chiasm or within the brainstem

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0, 1, or 2
• Ability to be treated with either a gamma knife or a linear accelerator-based radiosurgery system
• Willing and able to complete neurocognitive examination without assistance
• Willing and able to complete quality-of-life (QOL) questionnaires by themselves or with assistance
• Willing to provide mandatory blood and urine samples for correlative research purposes
• None of the following:
  • Pregnant or nursing
  • Men or women of childbearing potential who are unwilling to employ adequate contraception through out the study and for men for up to 3 months after completing treatment
• Able to complete a MRI with contrast of the head
• No known allergy to gadolinium

PRIOR CONCURRENT THERAPY:

• No prior cranial radiotherapy
• No planned cytotoxic chemotherapy during the stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT)
• Concurrent hormonal agents, steroids, and/or anticonvulsants allowed