CNS progression occurred in 9 of 450 ( 2.0 % ) and 3 of 446 ( 0.7 % ) patients without CNS metastases at baseline in the T-DM1 and XL arms , respectively , and in 10 of 45 ( 22.2 % ) and 8 of 50 ( 16.0 % ) patients with CNS metastases at baseline .