Put your itinerary in the trip planner or in railsaver (link is under the “booking” tab). That’s the best general recommendation you’re going to get. If you’re willing and able to buy non-refundable tickets from the individual national rail company websites you might be able to beat the railsaver price. However, it’s not always possible to buy all the tickets you need on-line due to credit card issues, some sites not selling international tickets, language issues and occasionally the need to have a paper ticket mailed to a European address. Buy your reservations at the train station in Europe — that will be significantly cheaper than any other method. It’s best to buy them at least a day in advance, but you can usually get them up to about 1 hour before train time. If you’re sure of the exact trains you want to take, you can buy them all in Brussels. Another option is to buy as you go. Buy the reservation you need for Brussels/Amsterdam before you leave the station when you arrive in Brussels from London. I would try to buy the Rome/Paris reservation before you get to Italy — there are sometimes lines to buy reservations in Italy. I only buy a reservation if the specific train I want to take requires it.

Is there are reason you’re doing roundtrip to London as opposed to an open jaw ticket?

I’d look for cheap flights or take overnight trains to/from Rome.