10. International normalized ratio (INR) ≤ 1.5 and activate partial thromboplastin time (aPTT) ≤ 1.5 x UNL 7 days previous to the first study drug administration, unless patients have been used prophylactic anticoagulant treatment 11. Patients with brain metastasis which had been treated and also asymptomatic , they are eligible to participate in the study.