This clinical trial was designed to investigate the efficiency and toxicity of fractionated stereotactic radiotherapy(FSRT) combined with Temozolomide(TMZ) for refractory brain metastases.

This is a single-arm, single center, phase II trial to investigate the feasibility and toxicity of FSRT plus TMZ for refractory brain metastases, which are defined as A: multiple brain metastases(≥3 lesions); B: large brain metastases(with one lesion's volume is no smaller than 6cc or the longest diameter is no shorter than 3cm); C: meningeal metastases.

Inclusion Criteria:

• Histologic or cytologic diagnosis of primary tumor and conformed brain metastases by enhanced MRI or CT
• the lesion number is no less than 3; or the tumor volume is no smaller than 6cc; or tumor diameter is no shorter than 3cm; or uncontrolled brain tumor after whole brain radiotherapy(WBRT); or the tumor is adjacent to essential structures of the brain, such as brain stem, optic chiasma, optic tract, etc.
• KPS ≥60，or KPS ≥40 and the limitation of motion is simply caused by brain tumor that is adjacent to the motor function areas.
• Age: 18-75 years old.
• Adequate end-organ function:

WBC≥4.0x109/L Neu ≥ 1.5x109/L Hemoglobin ≥ 110 g/L Platelets ≥100 x109/L Total bilirubin ≤ 1.5x ULN AST and ALT ≤ 1.5x ULN BUN and Cr: within the normal range

Exclusion Criteria:

• Other clinically significant diseases (e.g.myocardial infarction within the past 6 months, severe arrhythmia).
• Unable or unwilling to comply with the study protocol.
• The expected survival time is less than 3 months.
• Patients who are anticipated in other clinical trials of brain metastases.
• Patients who has been treated with SRT in other hospitals
• Pregnant patients or female patients whose HCG is positive
• Unsuitable to participate in study, that in the opinion of the treating physician.